Recent research has led to significant advances in our mechanistic understanding of mosquito-malaria parasite interactions, and yielded a number of novel approaches that could play a role in future vector control. The vast majority of this research has been conducted under standardized insectary conditions. Yet mosquitoes and parasites associate in a variable world. Our overall objective in the current proposal is to determine whether this miss-match between lab and field conditions matters. Specifically we aim to determine the extent to which realistic variation in environmental temperature affects the outcome of the mosquito-parasite interaction and the likely impact of two classes of prospective control tools. We will begin by quantifying the effects of different temperatures (both constant temperatures and realistic daily temperature variation) on a suite of mosquito (Anopheles stephensi) and parasite (Plasmodium falciparum) traits that combine to determine malaria transmission intensity. To complement these phenotypic measures and explore the mechanistic effects of temperature on mosquito and parasite physiology, we will use RNA sequencing to identify mosquito and parasite transcripts that correlate most strongly the mosquito and parasite traits that vary with changes in environmental temperature and infection status. We then will use qRT-PCR to examine at a finer scale how the expression dynamics of key mosquito and parasite genes change throughout the course of infection and across a range of environmental temperature treatments. Building on these baseline data, we will extend studies to evaluate the effects of temperature on the virulence of a fungal pathogen currently being developed for use as a biological pesticide against adult malaria vectors, and the transmission blocking potential of mosquitoes genetically modified to express novel anti-parasitic transgenes. Finally, we will use a suite of modeling approaches parameterized from the novel empirical data to explore the implications of environmental temperature for malaria transmission and control. Combined, the research will advance fundamental understanding of mosquito immune function and vector competence, better characterize the overall role of environmental temperature in the dynamics and distribution of malaria and provide an evidence base for appropriate development of innovative vector control tools.